Hyperexpansion of Functional Viral-Specific CD8+ T Cells in Lymphopenia-Associated MCMV Pneumonitis.

Published

Journal Article

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality in immunocompromised hosts, many of whom undergo significant periods of lymphopenia. However, the impact of lymphopenia and subsequent immune reconstitution on T cell responses and pulmonary pathology are poorly understood. Using a model of primary murine CMV infection in mice treated with cyclophosphamide (CY), the relationship of CD8+ T cell reconstitution to pneumonitis pathology was studied. Female BALB/c mice were infected with murine CMV (MCMV) with/without CY on day 1 post-infection. Lung pathology and viral specific T cell responses were assessed on days 7-28. T cell lymphocyte subsets, effector responses, and MCMV specificity were assessed at baseline and after in vitro stimulation of cells with immediate-early peptide pp89. CY treatment of MCMV-infected mice resulted in interstitial pneumonitis not seen with MCMV alone. Compared to MCMV alone, on day 14, MCMV/CY mice had greater number of CD8+ T cells, a fourfold increase in absolute number of pp89 tetramer-specific CD8+ cells, and an eightfold increase in MCMV specific T cell effector responses (IFN-γ; p<0.001). This expansion was preceded by transient lymphopenia, increased viral titers, and, most strikingly, a 10-fold increased proliferative capacity in MCMV/CY mice. In the setting of CY-associated lymphopenia, concurrent MCMV infection alters immune reconstitution toward a hyperexpanded MCMV-specific CD8+ effector T cell pool that correlates with significant lung immunopathology.

Full Text

Duke Authors

Cited Authors

  • Shah, PD; Zhong, Q; Lendermon, EA; Pipeling, MR; McDyer, JF

Published Date

  • June 2015

Published In

Volume / Issue

  • 28 / 5

Start / End Page

  • 255 - 264

PubMed ID

  • 26046830

Pubmed Central ID

  • 26046830

Electronic International Standard Serial Number (EISSN)

  • 1557-8976

Digital Object Identifier (DOI)

  • 10.1089/vim.2015.0005

Language

  • eng

Conference Location

  • United States